Photocontrol of cell adhesion mechanism

Agreement No.
1.1.1.5/21/A/003
Acronym
PhOAMS
Place of implementation of the project
LIOS, Aizkraukles iela 21, Riga, Latvia
Implementation period
01.06.2021. – 31.05.2023.
Project manager
Dr. Rossella Castagna
Total cost
140 202,24 EUR (ERDF funding – 119 171,90 EUR)
The aim of the project

Design of photocontrolled cell-cell adhesion protein modulators, using fragment-based drug discovery

Project activities
  • protein expression and purification;
  • structure based virtual screening (VS) and Fragment based drug discovery (FBDD);
  • design and synthesis of photoswitchable analogues of cell adhesion protein inhibitors;
  • characterization of complex protein-hit fragments;
  • design and production of biomimicking surfaces;
  • functional adhesion assays;
  • secondment, dissemination of scientific results and  communication to the general public.

The results of the study will be used to reiterate the relevance of the photopharmacology approach in biomedicine. The design of photocontrolled molecules for biomedical applications may lead to new drugs with limited side effects and enhanced specificity compared to current therapeutic agents.

Publication date 01.09.2021.

The project has started on 01.06.2021 and the operative plan has been discussed with the head of Biotechnology group which host the project.

 

The experimental activity continued with the design of bioinspired surfaces and the definition of criteria for the selection of the best experimental approach.

 

The training activity within WP1 led the principal investigator to complete the "Antimicrobial resistance" course organized by the Technical University of Denmark (DTU) and offered through Coursera (online course provider).

 

Publication in peer-reviewed international journal SN Comprehensive Clinical Medicine: International Scientific Collaboration Is Needed to Bridge Science to Society: USERN2020 Consensus Statement | SpringerLink
 

Publication date 01.09.2021.

The project activity continues with the design of biohybrid materials and photoswitchable compounds to modulate cell-cell adhesion. Regarding the development of photoswitchable drugs, the principal investigator signed a collaboration research agreement N 1.1.-5/28 with the Institute of Bioengineering of Catalonia, Barcelona (Spain) to carry out photopharmacological research in their facilities.

 

As part of the training activity planned in WP2, the principal investigator attended the Summer School on Drug Design (online mode) 13-17 September 2021 at the University of Vienna, focusing on pharmacoinformatics. As results of attendance to the school and poster presentation the principal investigator received 4 ECTS from the University of Vienna and expanded her competences on virtual screening and docking analysis.

 

The principal investigator delivered a poster presentation at the “EUROPIN Summer school on Drug Design- SSDD21 13-17 September 2021 (Online) titled: “Design of photoswitchable acetylcholinesterase inhibitors” and an invited talk at the USERN International Congress (online – Organized by Universal Scientific Education and Research Network (USERN)), 06-13 November 2021 titled “Biohybrid electrospun materials: the role of complex interfaces”(08.11.2021).

 

Publication date 30.11.2021.

On the 21st of February a review paper discussing, among other things, the field of photocontrol of protein-protein interactions in microtubule formation through photopharmacology has been accepted for publication in Frontiers in Molecular Bioscience. Susanna Eli*, Rossella Castagna*, Marina Mapelli, Emilio Parisini – “Recent approaches to the identification of novel microtubule-targeting agents” (DOI: 10.3389/fmolb.2022.841777)

*shared first authorship

Training activities have been followed on Circular Dichroism spectroscopy from Jasco company and Isothermal Titration Calorimetry (ITC) from Malvern company in the framework of the training activities on biophysical techniques (WP4).

Project PI attended the training course “Horizon Europe: Quick guide to tackle gender dimension and cross-cutting issues - Expert Insights” held by EMDESK Academy (10 February, 2022 Online).

Dissemination 11.02.2022: Project PI was a speaker for the International Day of Women in Science (11th February 2022) at a communication event organized by the Barcelona Institute of Science and Technology (BIST) delivering a talk on scientific activity and virtual guided lab tours targeting school students. (Online – Escola Gaspar, Barcelona - Spain).

 

Publication date 28.02.2022.

The experimental activity continued in the production and purification of the cell-adhesion proteins that will be used in the crystallization and ligand binding experiments. From the study of the structural characteristics of cell adhesion inhibitory molecules, suitable fragments have been identified for their engineering for the development of light-sensitive analogs. The synthesis of those light-sensitive compounds is currently underway.

On the 30th of March a review paper “Recent approaches to the identification of novel microtubule-targeting agents” has been published in Frontiers in Molecular Biosciences (9:841777 doi: 10.3389/fmolb.2022.841777) Susanna Eli, Rossella Castagna, Marina Mapelli, Emilio Parisini.

On the 4th of May, a project proposal has been submitted for the call Horizon Europe Pathfinder Open (Call: HORIZON-EIC-2022-PATHFINDEROPEN-01). Dr. Rossella Castagna is Head of Partner (LIOS) unit.

Dr. Rossella Castagna followed the webinar on IP in EU funded projects with a special focus on MSCA held by the European IP Helpdesk – on April 13th 2022.

Dr. Rossella Castagna completed the course “Master on EU Projects Design & Management 2021-2027” held by Europa Business School (Amsterdam) for a total of 40h lessons from January 2022 to May 2022.

Publication date 31.05.2022.

The scientific activity continued with the design and synthesis of photoswitchable compounds, as well as with their characterization. The design of photochromic analogues based on an azologization approach led to the definition of a successful synthetic route and a small library of compounds that are currently under investigation. The design has been conducted based on the results of virtual screening and docking experiments conducted previously.

 

Training activities

Dr. Castagna attended the workshop on “Molecular dynamics simulation with GROMACS” held at the LIOS by Dr. Nikhil Agrawal (June 27th – July 1st 2022).

 

Seminar

Dr. Castagna gave a seminar at the LIOS on “Electrospinning technique and applications” on the potentiality of the electrospinning technique to produce functional surfaces. June 13th 2022.

 

Conference presentation

Dr. Castagna attended the FEBS3+ Conference of the Estonian, Latvian and Lithuanian Biochemical Societies, organized by the Estonian Biochemical Society, Tallin (Estonia) 15-17 June 2022. At the conference, Dr. Castagna presented a poster on photopharmacology titled “Photoswitchable ligands as tools to modulate biological activity”.

 

International collaborations

A successful collaboration has been established with Prof. Elena Ishow from Nantes University (France) on the development of functional materials towards the removal of bacteria from water. The collaboration has led to a joint bilateral grant application between LIOS and Nantes University. Details are as follows: Project submitted for Latvian-French Hubert Curien partnership programme OSMOZE 2022. Bilateral project France (Nantes University - Prof. Elena Ishow) and Latvia (LIOS – Dr. Rossella Castagna).  Submitted on June 3rd 2022

 

Publications involving PhOAMS’s PI

  • A review paper describing the role of photopharmacology in animal behavior control has been published in the Journal of Molecular Neuroscience. Castagna R. et al. Orthogonal control of neuronal circuits and behavior using photopharmacology”.  J. Mol. Neurosci. 2022, 72, 1433–1442. https://doi.org/10.1007/s12031-022-02037-3 (Springer Nature, I.F. 3.4)
  • An original research paper on a new class of photoswitchable compounds applied for the first time in photopharmacology has been published in the Journal of American Chemical Society.  Castagna R. et al. Donor–Acceptor Stenhouse Adduct Displaying Reversible Photoswitching in Water and Neuronal Activity. J. Am. Chem. Soc. 2022, 144, 34, 15595–15602. DOI: 10.1021/jacs.2c04920 (ACS, I.F. 16.3)

Publication date 31.08.2022.